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1.
Free Radic Biol Med ; 190: 247-263, 2022 09.
Article in English | MEDLINE | ID: covidwho-2036015

ABSTRACT

Clinical studies have shown a significant positive correlation between age and the likelihood of being infected with SARS-CoV-2. This increased susceptibility is positively correlated with chronic inflammation and compromised neurocognitive functions. Postmortem analyses suggest that acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), with systemic and lung hyperinflammation, can cause significant morbidity and mortality in COVID-19 patients. Supraphysiological supplemental oxygen, also known as hyperoxia, is commonly used to treat decreased blood oxygen saturation in COVID-19 patients. However, prolonged exposure to hyperoxia alone can cause oxygen toxicity, due to an excessive increase in the levels of reactive oxygen species (ROS), which can overwhelm the cellular antioxidant capacity. Subsequently, this causes oxidative cellular damage and increased levels of aging biomarkers, such as telomere shortening and inflammaging. The oxidative stress in the lungs and brain can compromise innate immunity, resulting in an increased susceptibility to secondary lung infections, impaired neurocognitive functions, and dysregulated hyperinflammation, which can lead to ALI/ARDS, and even death. Studies indicate that lung inflammation is regulated by the central nervous system, notably, the cholinergic anti-inflammatory pathway (CAIP), which is innervated by the vagus nerve and α7 nicotinic acetylcholine receptors (α7nAChRs) on lung cells, particularly lung macrophages. The activation of α7nAChRs attenuates oxygen toxicity in the lungs and improves clinical outcomes by restoring hyperoxia-compromised innate immunity. Mechanistically, α7nAChR agonist (e.g., GAT 107 and GTS-21) can regulate redox signaling by 1) activating Nrf2, a master regulator of the antioxidant response and a cytoprotective defense system, which can decrease cellular damage caused by ROS and 2) inhibiting the activation of the NF-κB-mediated inflammatory response. Notably, GTS-21 has been shown to be safe and it improves neurocognitive functions in humans. Therefore, targeting the α7nAChR may represent a viable therapeutic approach for attenuating dysregulated hyperinflammation-mediated ARDS and sepsis in COVID-19 patients receiving prolonged oxygen therapy.


Subject(s)
Acute Lung Injury , COVID-19 , Hyperoxia , Pneumonia , Respiratory Distress Syndrome , Acute Lung Injury/metabolism , Aging , Antioxidants/metabolism , COVID-19/therapy , Humans , Hyperoxia/complications , Hyperoxia/metabolism , Lung/metabolism , Oxygen/metabolism , Pneumonia/metabolism , Reactive Oxygen Species/metabolism , SARS-CoV-2 , alpha7 Nicotinic Acetylcholine Receptor/metabolism
2.
Am J Physiol Heart Circ Physiol ; 323(3): H569-H576, 2022 09 01.
Article in English | MEDLINE | ID: covidwho-2001931

ABSTRACT

The post-acute phase of coronavirus disease 2019 (COVID-19) is often marked by several persistent symptoms and exertional intolerance, which compromise survivors' exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (V̇o2) kinetics and cardiopulmonary function in survivors of severe COVID-19 about 3-6 mo after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5 ± 1 mo after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximum-graded cardiopulmonary exercise test (CPX) with an initial 3-min period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). V̇o2 kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% (P = 0.008) and 28% (P = 0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed an 11% longer (P = 0.046) half-time of recovery of V̇o2 (T1/2V̇o2) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. Peak oxygen uptake (V̇o2peak), percent-predicted V̇o2peak, and V̇o2 at the ventilatory threshold (V̇o2VT) were reduced by 17%, 17%, and 12% in COVID-19 survivors, respectively (all P < 0.05). None of the ventilatory parameters differed between groups (all P > 0.05). In addition, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P < 0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which V̇o2 is adjusted to changes in energy demands.NEW & NOTEWORTHY Our findings provide novel data regarding the impact of COVID-19 on submaximal and maximal cardiopulmonary responses to exercise. We showed that V̇o2 kinetics is significantly impaired at both the onset (on-transient) and the recovery phase (off-transient) of exercise in these patients. Furthermore, our results suggest that survivors of severe COVID-19 may have a higher metabolic demand at a walking pace. These findings may partly explain the exertional intolerance frequently observed following COVID-19.


Subject(s)
COVID-19 , Oxygen Consumption , Cross-Sectional Studies , Exercise , Exercise Test/methods , Exercise Tolerance/physiology , Humans , Kinetics , Oxygen/metabolism , Oxygen Consumption/physiology , SARS-CoV-2 , Survivors
3.
Curr Opin Hematol ; 29(6): 306-309, 2022 11 01.
Article in English | MEDLINE | ID: covidwho-1973335

ABSTRACT

PURPOSE OF THE REVIEW: To discuss recent advances supporting the role of red blood cells (RBCs) in the host immune response. RECENT FINDINGS: Over the last century, research has demonstrated that red blood cells exhibit functions beyond oxygen transport, including immune function. Recent work indicates that the nucleic acid sensing receptor, toll-like receptor 9 (TLR9), is expressed on the RBC surface and implicated in innate immune activation and red cell clearance during inflammatory states. In addition to this DNA-sensing role of RBCs, there is growing evidence that RBCs may influence immune function by inducing vascular dysfunction. RBC proteomics and metabolomics have provided additional insight into RBC immune function, with several studies indicating changes to RBC membrane structure and metabolism in response to severe acute respiratory syndrome coronavirus 2 infection. These structural RBC changes may even provide insight into the pathophysiology of the 'long-coronavirus disease 2019' phenomenon. Finally, evidence suggests that RBCs may influence host immune responses via complement regulation. Taken together, these recent findings indicate RBCs possess immune function. Further studies will be required to elucidate better how RBC immune function contributes to the heterogeneous host response during inflammatory states. SUMMARY: The appreciation for nongas exchanging, red blood cell immune functions is rapidly growing. A better understanding of these RBC functions may provide insight into the heterogeneity observed in the host immune response to infection and inflammation.


Subject(s)
COVID-19 , Nucleic Acids , Erythrocytes/metabolism , Humans , Immunity , Nucleic Acids/metabolism , Oxygen/metabolism , Toll-Like Receptor 9/metabolism
4.
J Thromb Haemost ; 20(10): 2284-2292, 2022 10.
Article in English | MEDLINE | ID: covidwho-1949716

ABSTRACT

BACKGROUND: Erythrocyte aggregation is a phenomenon that is commonly found in several pathological disease states: stroke, myocardial infarction, thermal burn injury, and COVID-19. Erythrocyte aggregation is characterized by rouleaux, closely packed stacks of cells, forming three-dimensional structures. Healthy blood flow monodisperses the red blood cells (RBCs) throughout the vasculature; however, in select pathological conditions, involving hyperthermia and hypoxemia, rouleaux formation remains and results in occlusion of microvessels with decreased perfusion. OBJECTIVES: Our objective is to address the kinetics of rouleaux formation with sudden cessation of flow in variable temperature and oxygen conditions. METHODS: RBCs used in this in vitro system were obtained from healthy human donors. Using a vertical stop-flow system aligned with a microscope, images were acquired and analyzed for increased variation in grayscale to indicate increased aggregation. The onset of aggregation after sudden cessation of flow was determined at proscribed temperatures (37-49°C) and oxygen (0%, 10%), and in the presence and absence of 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS). Both autologous and homologous plasma were tested. RESULTS: RBCs in autologous plasma aggregate faster and with a higher magnitude with both hyperthermia and hypoxemia. Preventing deoxyhemoglobin from binding to band 3 with DIDS (dissociates the cytoskeleton from the membrane) fully blocks aggregation. Further, RBC aggregation magnitude is greater in autologous plasma. CONCLUSIONS: We show that the C-terminal domain of band 3 plays a pivotal role in RBC aggregation. Further, aggregation is enhanced by hyperthermia and hypoxemia.


Subject(s)
COVID-19 , Hyperthermia, Induced , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/metabolism , Erythrocyte Aggregation/physiology , Erythrocytes/metabolism , Humans , Hypoxia , Oxygen/metabolism
5.
PLoS One ; 17(5): e0268296, 2022.
Article in English | MEDLINE | ID: covidwho-1910641

ABSTRACT

Severe coronavirus disease-19 (COVID-19) is characterized by vascular inflammation and thrombosis. We and others have proposed that the inflammatory response to coronavirus infection activates endothelial cells, leading to endothelial release of pro-thrombotic proteins. These mediators can trigger obstruction of the pulmonary microvasculature, leading to worsening oxygenation, acute respiratory distress syndrome, and death. In the current study, we tested the hypothesis that higher levels of biomarkers released from endothelial cells are associated with worse oxygenation in patients with COVID-19. We studied 83 participants aged 18-84 years with COVID-19 admitted to a single center. The severity of pulmonary disease was classified by oxygen requirement, including no oxygen requirement, low-flow oxygen, high-flow nasal cannula oxygen, mechanical ventilation, and death. We measured plasma levels of two proteins released by activated endothelial cells, von Willebrand Factor (VWF) antigen and soluble P-Selectin (sP-Sel), and a biomarker of systemic thrombosis, D-dimer. Additionally, we explored the association of endothelial biomarker levels with the levels of pro-inflammatory cytokine and chemokines, and vascular inflammation biomarkers. We found that levels of VWF, sP-sel, and D-dimer were increased in individuals with more severe COVID-19 pulmonary disease. Biomarkers of endothelial cell activation were also correlated with proinflammatory cytokines and chemokines. Taken together, our data demonstrate increased levels of VWF and sP-selectin are linked to the severity of lung disease in COVID-19 and correlated with biomarkers of inflammation and vascular inflammation. Our data support the concept that COVID-19 is a vascular disease which involves endothelial injury in the context of an inflammatory state.


Subject(s)
COVID-19 , Thrombosis , Biomarkers , Chemokines/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Humans , Inflammation/metabolism , Oxygen/metabolism , Thrombosis/metabolism , von Willebrand Factor/metabolism
6.
Curr Protein Pept Sci ; 23(5): 310-320, 2022.
Article in English | MEDLINE | ID: covidwho-1892473

ABSTRACT

The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and associated hyper-inflammation due to exaggerated immune response. Different experimental and clinical studies revealed that many biomarkers could be used to determine the Covid-19 severity, such as Ddimer, procalcitonin, C-reaction protein (CRP), IL-6, and ferritin. Calprotectin (CP) is associated with intestinal inflammation, intestinal injury, and different respiratory diseases such as cystic fibrosis. Thus, CP might be a possible biomarker linking intestinal injury and acute lung injury (ALI) in Covid-19. Therefore, this study aimed to find a potential role of CP regarding GITI and ALI in Covid-19. CP is a complex protein consisting of S100A8 and S100A9, belonging to the Ca+2-binding proteins S100 family abundant in the cytosol of neutrophils and expressed on the monocyte membranes, macrophages, and intestinal epithelial cells. CP is a proinflammatory protein that acts through activation of the receptor for the advanced glycation end product (RAGE) and toll-like receptor 4 (TLR4). CP is a biomarker of neutrophil activation and is released following the turnover of neutrophils. CP could be controversial; it increases airway inflammation or protects lung and airway epithelium from an exaggerated immune response. Therefore, a high level of CP in different respiratory disorders might be protective and compensate against abnormal immune responses. CP level is high in Covid-19 and correlated with Covid-19 severity and oxygen demand due to activation of proinflammatory cytokines and inflammatory signaling pathways. Therefore, CP level is elevated in both ALI and intestinal inflammation so that it could be a potential biomarker that links the respiratory and intestinal injury in Covid-19.


Subject(s)
Acute Lung Injury , COVID-19 , Gastrointestinal Diseases , Leukocyte L1 Antigen Complex , Acute Lung Injury/virology , Biomarkers , COVID-19/complications , Cytokines/metabolism , Ferritins , Gastrointestinal Diseases/virology , Glycation End Products, Advanced/metabolism , Humans , Inflammation/metabolism , Interleukin-6/metabolism , Leukocyte L1 Antigen Complex/metabolism , Oxygen/metabolism , Procalcitonin/metabolism , SARS-CoV-2 , Toll-Like Receptor 4/metabolism
7.
Exp Physiol ; 107(7): 665-673, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1807292

ABSTRACT

NEW FINDINGS: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. ABSTRACT: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID-19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID-19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID-19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.


Subject(s)
COVID-19 , Sepsis , Adrenergic Agents/metabolism , Humans , Hypoxia , Lactate Dehydrogenases/metabolism , Lactic Acid/metabolism , Muscle, Skeletal/metabolism , Oxygen/metabolism , Sepsis/complications , Sepsis/diagnosis
8.
Can J Anaesth ; 67(10): 1393-1404, 2020 10.
Article in English | MEDLINE | ID: covidwho-1777843

ABSTRACT

Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure.


RéSUMé: Les complications pulmonaires du coronavirus (COVID-19) constituent ses manifestations cliniques les plus fréquentes. De récentes observations cliniques ont fait émerger deux phénotypes : le phénotype à élastance faible ou type L (low), et le phénotype à élastance élevée, ou type H (high). La présentation clinique, la physiopathologie, les mécanismes pulmonaires, ainsi que les observations radiologiques et échographiques de ces deux différents phénotypes sont différents. L'approche thérapeutique variera par conséquent selon le phénotype des patients atteints de COVID-19 souffrant d'insuffisance respiratoire.


Subject(s)
Coronavirus Infections/complications , Lung/diagnostic imaging , Pneumonia, Viral/complications , Respiratory Insufficiency/diagnostic imaging , Ultrasonography , Acute Disease , Algorithms , COVID-19 , Coronavirus Infections/diagnostic imaging , Humans , Lung/physiopathology , Lung/virology , Oxygen/metabolism , Pandemics , Phenotype , Pneumonia, Viral/diagnostic imaging , Point-of-Care Systems , Respiratory Insufficiency/virology , Respiratory Rate/physiology
10.
Int J Mol Sci ; 23(6)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1765732

ABSTRACT

Formation of neutrophil extracellular traps (NETs) is a two-faced innate host defense mechanism, which, on the one hand, can counteract microbial infections, but on the other hand, can contribute to massive detrimental effects on the host. Cholesterol depletion from the cellular membrane by Methyl-ß-cyclodextrin (MßCD) is known as one of the processes initiating NET formation. Since neutrophils mainly act in an inflammatory environment with decreased, so-called hypoxic, oxygen conditions, we aimed to study the effect of oxygen and the oxygen stress regulator hypoxia-inducible factor (HIF)-1α on cholesterol-dependent NET formation. Thus, murine bone marrow-derived neutrophils from wild-type and HIF-knockout mice or human neutrophils were stimulated with MßCD under normoxic (21% O2) compared to hypoxic (1% O2) conditions, and the formation of NETs were studied by immunofluorescence microscopy. We found significantly induced NET formation after treatment with MßCD in murine neutrophils derived from wild-type as well as HIF-1α KO mice at both hypoxic (1% O2) as well as normoxic (21% O2) conditions. Similar observations were made in freshly isolated human neutrophils after stimulation with MßCD or statins, which block the HMG-CoA reductase as the key enzyme in the cholesterol metabolism. HPLC was used to confirm the reduction of cholesterol in treated neutrophils. In summary, we were able to show that NET formation via MßCD or statin-treatment is oxygen and HIF-1α independent.


Subject(s)
Extracellular Traps , Animals , Cholesterol/metabolism , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mice , Neutrophils/metabolism , Oxygen/metabolism
11.
BMC Anesthesiol ; 22(1): 62, 2022 03 07.
Article in English | MEDLINE | ID: covidwho-1728877

ABSTRACT

BACKGROUND: The application of a surgical face mask over oxygen delivery devices is now a widespread recommendation in the setting of the Coronavirus disease pandemic. This addition is designed to reduce droplet spread, but this also changes the nature of these devices, and may alter the amount of oxygen delivered to a patient. This research investigated how placing a surgical face mask over both a simple plastic mask ("Hudson mask") and nasal cannula altered the concentration of available oxygen measured at the nares. METHODS: We measured the inspired and end-tidal oxygen concentrations of five healthy non-smoking volunteers. Oxygen was delivered via nasal cannula and also a simple plastic face mask, at flow rates of 2, 4, 6 and 8 l per minute, with and without an overlying surgical face mask. RESULTS: Adding a surgical mask over nasal cannula caused an appreciable rise in the end-tidal oxygen concentrations at all the measured oxygen flow rates 2, 4, 6, 8 L/minute. With the Hudson mask, there was a rise in oxygen concentration at 4 and 6 L/minute. For example, at a flow rate of 4 l/min via nasal cannula, available oxygen concentration increased from 24 to 36%, and via the Hudson mask the concentration rose from 27 to 38%. CONCLUSIONS: The addition of a surgical face mask over both nasal cannula and a Hudson mask resulted in an increased available oxygen concentration. This may be valuable where more advanced oxygen devices are not available, or alternatively providing adequate supplemental oxygen at lower flow rates and thus making critical savings in oxygen usage.


Subject(s)
Masks , Oxygen Inhalation Therapy/instrumentation , Oxygen Inhalation Therapy/methods , Oxygen/administration & dosage , Oxygen/metabolism , Adult , Cannula , Cross-Over Studies , Female , Healthy Volunteers , Humans , Male , Nasal Cavity , Reference Values
12.
Am J Respir Cell Mol Biol ; 66(3): 323-336, 2022 03.
Article in English | MEDLINE | ID: covidwho-1714501

ABSTRACT

Administration of high concentrations of oxygen (hyperoxia) is one of few available options to treat acute hypoxemia-related respiratory failure, as seen in the current coronavirus disease (COVID-19) pandemic. Although hyperoxia can cause acute lung injury through increased production of superoxide anion (O2•-), the choice of high-concentration oxygen administration has become a necessity in critical care. The objective of this study was to test the hypothesis that UCP2 (uncoupling protein 2) has a major function of reducing O2•- generation in the lung in ambient air or in hyperoxia. Lung epithelial cells and wild-type; UCP2-/-; or transgenic, hTrx overexpression-bearing mice (Trx-Tg) were exposed to hyperoxia and O2•- generation was measured by using electron paramagnetic resonance, and lung injury was measured by using histopathologic analysis. UCP2 expression was analyzed by using RT-PCR analysis, Western blotting analysis, and RNA interference. The signal transduction pathways leading to loss of UCP2 expression were analyzed by using IP, phosphoprotein analysis, and specific inhibitors. UCP2 mRNA and protein expression were acutely decreased in hyperoxia, and these decreases were associated with a significant increase in O2•- production in the lung. Treatment of cells with rhTrx (recombinant human thioredoxin) or exposure of Trx-Tg mice prevented the loss of UCP2 protein and decreased O2•- generation in the lung. Trx is also required to maintain UCP2 expression in normoxia. Loss of UCP2 in UCP2-/- mice accentuated lung injury in hyperoxia. Trx activates the MKK4-p38MAPK (p38 mitogen-activated protein kinase)-PGC1α (PPARγ [peroxisome proliferator-activated receptor γ] coactivator 1α) pathway, leading to rescue of UCP2 and decreased O2•- generation in hyperoxia. Loss of UCP2 in hyperoxia is a major mechanism of O2•- production in the lung in hyperoxia. rhTrx can protect against lung injury in hyperoxia due to rescue of the loss of UCP2.


Subject(s)
Lung/metabolism , Oxygen/metabolism , Thioredoxins/metabolism , Uncoupling Protein 2/metabolism , Animals , COVID-19/metabolism , COVID-19/therapy , Cell Line , Humans , Hyperoxia/metabolism , Lung/cytology , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase 4/metabolism , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Oxygen/toxicity , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Phosphorylation , Signal Transduction , Superoxides/metabolism , Thioredoxins/genetics , Thioredoxins/pharmacology , Uncoupling Protein 2/genetics , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
13.
BJOG ; 129(3): 493-499, 2022 02.
Article in English | MEDLINE | ID: covidwho-1636549

ABSTRACT

OBJECTIVE: To study the effect of delivery on the pO2 /FiO2 ratio (P/F ratio) in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and to compare characteristics between delivered and undelivered pregnant patients with COVID-19. DESIGN: Retrospective cohort. SETTING: Four hospitals in Houston, Texas. POPULATION: Pregnant patients admitted to the hospital for COVID-19. METHODS: Among patients with ARDS who were delivered during their hospitalisation for COVID-19, linear mixed models were used to investigate time trends before and after delivery of the P/F ratio. Patient characteristics were compared between patients delivered during their hospitalisation for COVID-19 and those discharged undelivered. MAIN OUTCOME MEASURES: The P/F ratio, age, gestational age, length of stay and severity of illness, RESULTS: Between 4 May 2020 and 26 July 2020, a total of 61 pregnant patients were admitted for COVID-19. Baseline characteristics were similar between the study groups. Delivery occurred in 21 (34%) of patients during their hospitalisation for COVID-19. Delivered patients had more severe disease and were admitted at a later gestational age than patients not delivered. Ten of these 21 patients (48%) were delivered preterm; of these, six were delivered due to complications of COVID-19 and four were delivered for obstetric indications. In patients with ARDS who were delivered (n = 17), the P/F ratio had a negative slope that improved after delivery. CONCLUSIONS: COVID-19-related ARDS in pregnancy requires multidisciplinary care and individualised decision-making, but delivery slows the deterioration of the P/F ratio in these patients. TWEETABLE ABSTRACT: Delivery improves the P/F ratio in COVID-19-related ARDS, though individualised delivery management is needed.


Subject(s)
COVID-19/epidemiology , Carbon Dioxide/metabolism , Delivery, Obstetric/statistics & numerical data , Oxygen/metabolism , Adult , COVID-19/therapy , Female , Gestational Age , Humans , Pandemics , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/therapy , Retrospective Studies , SARS-CoV-2
15.
Respir Med ; 189: 106638, 2021.
Article in English | MEDLINE | ID: covidwho-1517456

ABSTRACT

BACKGROUND: High-Flow Nasal Cannula (HFNC) therapy is useful treatment in patients with acute respiratory failure (ARF). The ROX index (ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate) has been evaluated to predict success of HFNC in patients with pneumonia. OBJECTIVE: The aim of this study was to determine whether the ROX Index could predict HFNC therapy success in patients with ARF due to SARS-CoV-2 pneumonia. METHODS: An observational, prospective study was performed including patients admitted with ARF secondary to SARS-CoV-2 pneumonia who met criteria for HFNC therapy initiation. Demographic, radiological, laboratory and clinical course data were collected. The ROX index was calculated at 1 h, 6 h, 12 h and 24 h after starting HFNC. RESULTS: In total 85 patients were included (age, 64.51 + 11.78 years; male, 69.4%). HFNC failed in 47 (55.3%) patients, of whom 45 (97.8%) were initially managed with noninvasive ventilation (NIV). ROX index at 24 h was the best predictor of HFNC success (AUC 0.826, 95%CI 0.593-1.00, p = 0.015) with a cut-off point of 5.35 (S 0.91, Sp 0.79, PPV 0.92, NPP 0.79). In multivariate logistic regression analysis ROX index at 24 h proved the best predictor of HFNC success. CONCLUSIONS: ROX index at 24 h with a cut-off point of 5.35 predicts HFNC success in patients with SARS-Cov-2-induced ARF.


Subject(s)
COVID-19/complications , Oximetry , Oxygen Inhalation Therapy , Oxygen/metabolism , Respiratory Insufficiency/therapy , Respiratory Rate , Female , Humans , Male , Middle Aged , Noninvasive Ventilation , Prospective Studies
16.
Sci Rep ; 11(1): 21124, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1493211

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.


Subject(s)
COVID-19/diagnosis , COVID-19/mortality , Intubation, Intratracheal/methods , Severity of Illness Index , Adolescent , Adult , Age Factors , Aged , Arterial Pressure , COVID-19/therapy , Female , Ferritins/blood , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , New York , Nitrogen/metabolism , Oxygen/metabolism , Predictive Value of Tests , ROC Curve , Regression Analysis , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Vasoconstrictor Agents/pharmacology , Young Adult
17.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: covidwho-1486398

ABSTRACT

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.


Subject(s)
Brain/physiology , Masks , Activities of Daily Living , Adult , Brain/blood supply , Brain/metabolism , COVID-19/prevention & control , Female , Healthy Volunteers , Hemodynamics , Humans , Male , Microcirculation , Monitoring, Physiologic , Oxygen/metabolism , SARS-CoV-2 , Spectroscopy, Near-Infrared , Young Adult
18.
Anaesthesia ; 76(11): 1546-1547, 2021 11.
Article in English | MEDLINE | ID: covidwho-1455502
19.
Pan Afr Med J ; 39: 203, 2021.
Article in English | MEDLINE | ID: covidwho-1404090

ABSTRACT

INTRODUCTION: the COVID-19 pandemic has necessitated the prolonged use of facemasks by healthcare workers. Facemask non-compliance has been largely blamed on discomfort associated with the mask, and apprehension regarding potential health hazards such as asphyxia from mask usage. We sought to evaluate the impact of different respiratory mask types on the comfort of healthcare workers and their arterial oxygen saturation during periods of active clinical duty. METHODS: we conducted a cross-sectional study on healthcare workers donning different types of facemasks in the normal course of duty. Objective non-invasive determination of arterial oxygen saturation of each participant was done using a portable pulse oximeter. Subjective self-assessment of global discomfort was scored by means of a 11-point numerical scale from 0 (no discomfort) to 10 (worst discomfort imaginable). The user's perceived elements of the discomfort were also evaluated. A statistical significance was accepted when P <0.05. RESULTS: seventy-six healthcare workers completed the study, and wore the masks for periods ranging from 68-480 minutes. The discomfort experienced with the use of the N95 mask; 4.3 (2.0) was greater than the surgical mask; 2.7 (1.8); P=0.001. No significant change in arterial oxygen saturation was observed with the use of either of the mask types. The tight strapping of the N95 mask was perceived as a contributor to the discomfort experienced with mask usage; P=0.009. CONCLUSION: the N95 masks imposed greater discomfort than the surgical masks, but neither of the masks impacted on the arterial oxygen saturation of the healthcare workers.


Subject(s)
COVID-19 , Health Personnel/psychology , Masks/adverse effects , Oxygen/metabolism , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , N95 Respirators/adverse effects , Oximetry , Time Factors
20.
PLoS One ; 16(2): e0247414, 2021.
Article in English | MEDLINE | ID: covidwho-1388900

ABSTRACT

BACKGROUND: Facemasks are recommended to reduce the spread of SARS-CoV-2, but concern about inadequate gas exchange is an often cited reason for non-compliance. RESEARCH QUESTION: Among adult volunteers, do either cloth masks or surgical masks impair oxygenation or ventilation either at rest or during physical activity? STUDY DESIGN AND METHODS: With IRB approval and informed consent, we measured heart rate (HR), transcutaneous carbon dioxide (CO2) tension and oxygen levels (SpO2) at the conclusion of six 10-minute phases: sitting quietly and walking briskly without a mask, sitting quietly and walking briskly while wearing a cloth mask, and sitting quietly and walking briskly while wearing a surgical mask. Brisk walking required at least a 10bpm increase in heart rate. Occurrences of hypoxemia (decrease in SpO2 of ≥3% from baseline to a value of ≤94%) and hypercarbia (increase in CO2 tension of ≥5 mmHg from baseline to a value of ≥46 mmHg) in individual subjects were collected. Wilcoxon signed-rank was used for pairwise comparisons among values for the whole cohort (e.g. walking without a mask versus walking with a cloth mask). RESULTS: Among 50 adult volunteers (median age 33 years; 32% with a co-morbidity), there were no episodes of hypoxemia or hypercarbia (0%; 95% confidence interval 0-1.9%). In paired comparisons, there were no statistically significant differences in either CO2 or SpO2 between baseline measurements without a mask and those while wearing either kind of mask mask, both at rest and after walking briskly for ten minutes. INTERPRETATION: The risk of pathologic gas exchange impairment with cloth masks and surgical masks is near-zero in the general adult population.


Subject(s)
COVID-19/prevention & control , Masks , Oxygen/metabolism , Pulmonary Ventilation/physiology , Adult , COVID-19/psychology , COVID-19/transmission , Carbon Dioxide/metabolism , Exercise/physiology , Female , Heart Rate/physiology , Humans , Hypoxia/etiology , Hypoxia/metabolism , Male , Masks/adverse effects , N95 Respirators/adverse effects , Rest/physiology , SARS-CoV-2/isolation & purification , Walking/physiology
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